Napoli put out a full-strength side, but Milan miss Alessio Romagnoli as the Partenopei aim to overtake Juventus.
It kicks off at the Stadio San Paolo at 20.00 GMT, follow the build-up and action on our LIVEBLOG.
As Juve were held 0-0 by Bologna on Friday evening, a victory would allow Napoli to leapfrog them and recapture the Serie A leadership.
However, the Rossoneri are one of the form teams right now and need a result of their own to stay in the hunt for Europe.
When these sides last met on October 4, Napoli ran out 4-0 winners at San Siro, including a Lorenzo Insigne brace.
Milan have changed considerably since then, losing just two of their last 19 competitive games and unbeaten since January 6.
Maurizio Sarri’s men were in action on Thursday evening, losing 1-0 at Villarreal in the Europa League Round of 32.
Jorginho didn’t even make that trip to due flu symptoms, while Insigne, Gonzalo Higuain, Allan, Raul Albiol and Faouzi Ghoulam all return to the starting XI.
Milan have Ignazio Abate and Juraj Kucka back from injury, but centre-back Alessio Romagnoli has been suffering from flu and is only fit for the bench, so Cristian Zapata starts.
This will be a fascinating battle between two of Serie A’s most ruthless marksmen, Carlos Bacca and Pipita Higuain.
There is also the pace of M’Baye Niang and Jose Callejon.
Napoli: Reina; Hysaj, Albiol, Koulibaly, Ghoulam; Allan, Jorginho, Hamsik; Callejon, Higuain, Insigne
Napoli bench: Rafael, Gabriel, Maggio, Chiriches, Regini, Strinic, David Lopez, Valdifiori, Chalobah, El Kaddouri, Gabbiadini, Mertens
Milan: Donnarumma; Abate, Alex, Zapata, Antonelli; Honda, Kucka, Montolivo, Bonaventura; Bacca, Niang
Milan bench: Abbiati, Livieri, Calabria, De Sciglio, Romagnoli, Poli, Locatelli, José Mauri, Simic, Boateng, Bertolacci, Menez, Balotelli